ArticleCancer cell2023
Loss of SYNCRIP unleashes APOBEC-driven mutagenesis, tumor heterogeneity, and AR-targeted therapy resistance in prostate cancer.
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Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 45 citations in OpenAlex.
- PABPC1 dictates castration sensitivity in prostate cancer via orchestrating ferroptosis resistance and CD8(+) T-cell dysfunction.Cell death and differentiation · 2026Article
- CRISPR decodes the RNA regulatory network in prostate cancer: A review from mechanisms to precision therapeutics.Non-coding RNA research · 2026Review
- The regulatory mechanism and clinical significance of RNA editing in prostate cancer.Current urology · 2026Review
- Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Ferroptosis vulnerability of enzalutamide resistant prostate cancer conferred by ACSL4 overexpression and GPX4 antagonism.Cell death & disease · 2026Article
- Game of clones: decipher lineage plasticity in hormone-driven cancers.Cellular and molecular life sciences : CMLS · 2026Review
- Histone deacetylases: Function in tumor development and therapeutic prospects (Review).Oncology letters · 2026Review
- Integrated Genomic and Single-Cell Analysis Reveals Heterogeneity, Prognosis, and Treatment Vulnerability in Urothelial Carcinoma.Human mutation · 2026Article
- SYNCRIP drives ferroptosis resistance and metabolic activation via SIRT1 and HK2 in glioblastoma.International journal of biological sciences · 2026Article
- A novel polyester-drug nanoconjugate with subtype selectivity for high efficacy against PSMA-positive prostate cancer.Regenerative biomaterials · 2026Article
- ATHENA: A deep learning-based AI for functional prediction of genomic mutations and synergistic vulnerabilities in prostate cancer.bioRxiv : the preprint server for biology · 2025Article
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Unveiling the Genetic Mosaic of Pediatric AML: Insights from Southwest China.Current oncology (Toronto, Ont.) · 2025Article
- BRCA2 deficiency and replication stress drive APOBEC3-Mediated genomic instability.Nature communications · 2025Article
- TRIM35, a novel DNA-binding protein, epigenetically modifies H3 to promote HSPA6 transcription and suppress breast cancer progression.Cell death discovery · 2025Article
- APOBEC3A-Induced DNA Damage Drives Polymerase θ Dependency and Synthetic Lethality in Cancer.bioRxiv : the preprint server for biology · 2025Article
- Combined SNPs sequencing and allele specific proteomics capture reveal functional causality underpinning the 2p25 prostate cancer susceptibility locus.Nature communications · 2025Article
- Treatment-related mutagenic processes in acute lymphoblastic leukemia.Haematologica · 2025Review
- Comprehensive Insights into APOBEC Mutations in Thyroid Cancer: Prognostic and Therapeutic Discoveries.Biological procedures online · 2025Article
- Multi-omics analysis of the effects of pla2g4a on the prognosis of various cancers and its experimental validation in breast cancer cell lines.Discover oncology · 2025Article
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Authors and funding
31 authors at 5 institutions in 2 countries.
Xiaoling LiDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Yunguan WangQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA; Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Su DengDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Guanghui ZhuDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada.
Choushi WangDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Nickolas A JohnsonDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Zeda ZhangHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Carla Rodriguez TiradoDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Yaru XuDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Lauren A MetangDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Julisa GonzalezDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Atreyi MukherjiDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Jianfeng YeLyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.
Yuqiu YangQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA.
Wei PengDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Yitao TangDepartment of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX, USA.
Mia HofstadDepartment of Urology, UT Southwestern Medical Center, Dallas, TX, USA.
Zhiqun XieQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA.
Heewon YoonDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA.
Liping ChenDepartment of Urology, UT Southwestern Medical Center, Dallas, TX, USA.
Xihui LiuDepartment of Urology, UT Southwestern Medical Center, Dallas, TX, USA.
Sujun ChenDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada.
Hong ZhuQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
Douglas StrandDepartment of Urology, UT Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
Han LiangDepartment of Bioinformatics and Computational Biology, MD Anderson Cancer Center, Houston, TX, USA; Department of Systems Biology, MD Anderson Cancer Center, Houston, TX, USA.
Ganesh RajDepartment of Urology, UT Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA.
Housheng Hansen HeDepartment of Medical Biophysics, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Center, University Health Network, Toronto, ON, Canada.
Joshua T MendellDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA; Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Bo LiLyda Hill Department of Bioinformatics, UT Southwestern Medical Center, Dallas, TX, USA.
Tao WangQuantitative Biomedical Research Center, Peter O'Donnell Jr. School of Public Health, UT Southwestern Medical Center, Dallas, TX, USA.
Ping MuDepartment of Molecular Biology, UT Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA; Hamon Center for Regenerative Science and Medicine, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: ping.mu@utsouthwestern.edu.
Southwestern Medical Center · USUniversity Health Network · CAMemorial Sloan Kettering Cancer Center · USCincinnati Children's Hospital Medical Center · USThe University of Texas MD Anderson Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MUT Southwestern Medical Center Simmons Comprehensive Cancer CenterP30CA142543 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sandi Leigh Pruitt · 2010 to 2026
$53.7MUT Southwestern NORCP30DK127984 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI JAY D. HORTON · 2022 to 2026
$7.4MCancer Biology Training GrantT32CA124334 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI SHAY, JERRY WILLIAM · 2007 to 2021
$5.3MThe intersection of RNA biology and tumor biologyR35CA197311 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MENDELL, JOSHUA T · 2015 to 2021
$5.1MElucidating the Molecular Role of SYNCRIP in Prostate Cancer and AR Targeted Therapy ResistanceR37CA258730 · NCI · YALE UNIVERSITY · PI Ping Mu · 2021 to 2026
$2.7MThe role of long noncoding RNA CRNDE in normal physiology and cancerR01CA282036 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Joshua T Mendell · 2023 to 2026
$1.9MAntigen-independent prediction and biomarker identification of cancer-specific T cellsR01CA245318 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI LI, BO · 2020 to 2024
$1.9MApplying deep learning to predict T cell receptor binding specificity of neoantigens and response to checkpoint inhibitorsR01CA258584 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI WANG, TAO, WANG, XINLEI · 2021 to 2025
$1.4MOvercome the lineage plasticity conferred targeted therapy resistance in advanced prostate cancerR00CA218885 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI MU, PING · 2018 to 2020
$719kRole of the tumor microenvironment in promoting drug resistance in castration resistant prostate cancerF99CA223063 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ZHANG, ZEDA · 2017 to 2018
$90kDissecting the role of UBE2J1 in prostate cancerF31CA261019 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI RODRIGUEZ-TIRADO, CARLA SOFIA · 2022 to 2023
$57kHoward Hughes Medical InstituteNCI NIH HHS F31 CA261019NCI NIH HHS F99 CA223063NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA142543NCI NIH HHS R00 CA218885NCI NIH HHS R01 CA245318NCI NIH HHS R01 CA258584NCI NIH HHS R35 CA197311NCI NIH HHS R37 CA258730NCI NIH HHS T32 CA124334NIDDK NIH HHS P30 DK127984
Abstract
Tumor mutational burden and heterogeneity has been suggested to fuel resistance to many targeted therapies. The cytosine deaminase APOBEC proteins have been implicated in the mutational signatures of more than 70% of human cancers. However, the mechanism underlying how cancer cells hijack the APOBEC mediated mutagenesis machinery to promote tumor heterogeneity, and thereby foster therapy resistance remains unclear. We identify SYNCRIP as an endogenous molecular brake which suppresses APOBEC-driven mutagenesis in prostate cancer (PCa). Overactivated APOBEC3B, in SYNCRIP-deficient PCa cells, is a key mutator, representing the molecular source of driver mutations in some frequently mutated genes in PCa, including FOXA1, EP300. Functional screening identifies eight crucial drivers for androgen receptor (AR)-targeted therapy resistance in PCa that are mutated by APOBEC3B: BRD7, CBX8, EP300, FOXA1, HDAC5, HSF4, STAT3, and AR. These results uncover a cell-intrinsic mechanism that unleashes APOBEC-driven mutagenesis, which plays a significant role in conferring AR-targeted therapy resistance in PCa.
Indexed as
Prostatic NeoplasmsBromodomain Containing ProteinsChromosomal Proteins, Non-HistoneCytidine DeaminaseHeterogeneous-Nuclear RibonucleoproteinsHumansMaleMinor Histocompatibility AntigensMutagenesisMutationPolycomb Repressive Complex 1Receptors, AndrogenAPOBEC3B protein, humanBRD7 protein, humanBromodomain Containing ProteinsCBX8 protein, humanChromosomal Proteins, Non-HistoneCytidine DeaminaseHeterogeneous-Nuclear RibonucleoproteinsMinor Histocompatibility AntigensPolycomb Repressive Complex 1Receptors, AndrogenSYNCRIP protein, humanantiandorgenAPOBECAR-targeted therapy resistanceEP300FOXA1mutagenesisprostate cancerSYNCRIPtumor heterogeneity
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